title: IL-1 alpha and TNF-alpha are required for IL-12-induced development of Th1 cells producing high levels of IFN-gamma in BALB/c but not C57BL/6 mice.
abstract: The development of Th1- or Th2-type responses determines the type of immune response that is elicited in response to Ag. Responsiveness to IL-12 is critical for the development of Th1-type CD4+ T cells required for cell-mediated immune responses. Addition of IL-12 to primary cultures of CD4+ T cells stimulated with OVA and splenocytes or dendritic cells resulted in the development of a Th1 phenotype with the capacity to secrete high levels of IFN-gamma upon restimulation with splenic APC. The present study shows that using dendritic cells to present Ag upon restimulation reveals a requirement for additional cofactors, including IL-1 alpha and TNF-alpha, which were provided by spleen cells but not dendritic cells. Furthermore, these cofactors are required for optimal IL-12-induced Th1 development in BALB/c but not C57BL/6 mice. This differential requirement for such cofactors in IL-12-driven Th1 development may play a role in genetic predisposition to Th1 or Th2 responses to infectious agents.
authors.affiliation: Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, CA 94303, USA.
authors.forename: K
authors.initials: K
authors.lastname: Shibuya
authors.forename: D
authors.initials: D
authors.lastname: Robinson
authors.forename: F
authors.initials: F
authors.lastname: Zonin
authors.forename: S B
authors.initials: SB
authors.lastname: Hartley
authors.forename: S E
authors.initials: SE
authors.lastname: Macatonia
authors.forename: C
authors.initials: C
authors.lastname: Somoza
authors.forename: C A
authors.initials: CA
authors.lastname: Hunter
authors.forename: K M
authors.initials: KM
authors.lastname: Murphy
authors.forename: A
authors.initials: A
authors.lastname: O'Garra
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D017635:Clonal Anergy / Q000235:genetics; D002999:Clone Cells; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000502:physiology*; D018664:Interleukin-12 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma